Infection of Glia by Human Pegivirus Suppresses Peroxisomal and Antiviral Signaling Pathways.

Human pegivirus (HPgV) infects peripheral leukocytes but was recently shown to be a neurotropic virus associated with leukoencephalitis in humans. In the present study, we investigated the neural cell tropism of HPgV as well as its effects on host immune responses. HPgV wild type (WT) and a mutant virus with a deletion in the HPgV NS2 gene (ΔNS2) were able to productively infect human astrocytes and microglia but not neurons or an oligodendrocyte-derived cell line. Of note, the ΔNS2 virus replicated better than WT pegivirus in astrocytes, with both viruses being able to subsequently infect and spread in fresh human astrocyte cultures. Infection of human glia by HPgV WT and ΔNS2 viruses resulted in suppression of peroxisome-associated genes, including PEX11B, ABCD1, PEX7, ABCD3, PEX3, and PEX5L, during peak viral production, which was accompanied by reduced expression of IFNB, IRF3, IRF1, and MAVS, particularly in ΔNS2-infected cells. These data were consistent with analyses of brain tissue from patients infected with HPgV in which we observed suppression of peroxisome and type I interferon gene transcripts, including PEX11B, ABCD3, IRF1, and IRF3, with concurrent loss of PMP70 immunoreactivity in glia. Our data indicate that human astrocytes and microglia are permissive to HPgV infection, resulting in peroxisome injury and suppressed antiviral signaling that is influenced by viral diversity. IMPORTANCE Human pegiviruses are detected in 1 to 5% of the general population, principally infecting leukocytes, although their effects on human health remain uncertain. Here, we show that human pegivirus infects specific neural cell types in culture and human brain and, like other neurotropic flaviviruses, causes suppression of peroxisome and antiviral signaling pathways, which could favor ongoing viral infection and perhaps confer susceptibility to the development of neurological disease.

The initial soil microbiota impacts the potential for lignocellulose degradation during soil solarization.

AIMS: Soil biosolarization (SBS) is a pest control technology that includes the incorporation of organic matter into soil prior to solarization. The objective of this study was to measure the impact of the initial soil microbiome on the temporal evolution of genes encoding lignocellulose-degrading enzymes during SBS. METHODS AND RESULTS: Soil biosolarization field experiments were completed using green waste (GW) as a soil amendment and in the presence and absence of compost activating inoculum. Samples were collected over time and at two different soil depths for measurement of the microbial community and the predicted lignocellulosic-degrading microbiome. Compost inoculum had a significant positive effect on several predicted genes encoding enzymes involved in cellulose, hemicellulose and lignin degradation. These included beta-glucosidase, endo-1,3(4)-beta-glucanase, alpha-galactosidase and laccase. CONCLUSION: Amendment of micro-organisms found in compost to soil prior to SBS enhanced the degradation potential of cellulose, hemicellulose and lignin found in GW. SIGNIFICANCE AND IMPACT OF THE STUDY: The type of organic matter amended and its biotransformation by soil micro-organisms impact the efficacy of SBS. The results suggest that co-amending highly recalcitrant biomass with micro-organisms found in compost improves biomass conversion during SBS.

First evaluation of the Behavioral Addiction Indoor Tanning Screener (BAITS) in a nationwide representative sample.

BACKGROUND: Evidence suggests that indoor tanning may have addictive properties. However, many instruments for measuring indoor tanning addiction show poor validity and reliability. Recently, a new instrument, the Behavioral Addiction Indoor Tanning Screener (BAITS), has been developed. OBJECTIVES: To test the validity and reliability of the BAITS by using a multimethod approach. METHODS: We used data from the first wave of the National Cancer Aid Monitoring on Sunbed Use, which included a cognitive pretest (August 2015) and a Germany-wide representative survey (October to December 2015). In the cognitive pretest 10 users of tanning beds were interviewed and 3000 individuals aged 14-45 years were included in the representative survey. Potential symptoms of indoor tanning addiction were measured using the BAITS, a brief screening survey with seven items (answer categories: yes vs. no). Criterion validity was assessed by comparing the results of BAITS with usage parameters. Additionally, we tested internal consistency and construct validity. RESULTS: A total of 19·7% of current and 1·8% of former indoor tanning users were screened positive for symptoms of a potential indoor tanning addiction. We found significant associations between usage parameters and the BAITS (criterion validity). Internal consistency (reliability) was good (Kuder-Richardson-20, 0·854). The BAITS was shown to be a homogeneous construct (construct validity). CONCLUSIONS: Compared with other short instruments measuring symptoms of a potential indoor tanning addiction, the BAITS seems to be a valid and reliable tool. With its short length and the binary items the BAITS is easy to use in large surveys.

The Effect of Losses Disguised as Wins and Near Misses in Electronic Gaming Machines: A Systematic Review.

Near misses and losses disguised as wins have been of interest to gambling researchers and policymakers for many years (e.g., Griffiths in J Gambl Stud 9(2):101-120, 1993). This systematic literature review describes the behavioural, psychological, and psychobiological effects of near misses and losses disguised as wins (LDWs) in an effort to evaluate their precise influence on the player and to highlight areas requiring further investigation. A systematic search for relevant studies was conducted using Scopus, PubMed, PsycINFO, ProQuest Sociology databases, and the Gambling Research Exchange Ontario Knowledge Repository. A total of 51 (from an initial pool of 802) experimental peer-reviewed studies using human participants were found between 1991 and 2015. The systematic review revealed that near misses motivate continued play, but have varying effects on the emotional state or betting behaviour of the player. Near miss events were also shown to be associated with elevated skin conductance levels and diffuse activity across the brain, most consistently in areas processing reinforcement and reward. Re-examination of the studies of near misses events after classifying the type of game feedback suggested that the effectiveness of near misses is related to the phenomenology of a near miss itself rather than as a response to auditory or visual feedback provided by a slot machine. In contrast to near misses, the presence of LDWs was found to relate to an overestimation of how much a player is actually winning and was consistently viewed as an exciting event. The effect of LDWs appears to be driven by the presence of visuals and sounds most often associated with a true win. Practical implications and directions for future research are also discussed.

Transmission of GB virus type C via transfusion in a cohort of HIV-infected patients.

BACKGROUND: GB virus C (GBV-C) infection is transmitted by blood exposure and associated with lower human immunodeficiency virus (HIV) load and slower HIV disease progression. Few studies describe predictors of acute GBV-C infection following transfusion in HIV-infected patients. METHODS: We used a limited-access database from the National Heart Lung and Blood Institute's Viral Activation Transfusion Study, a randomized controlled trial of leukoreduced versus nonleukoreduced transfusions received by HIV-infected, transfusion-naive patients. Blood samples from 489 subjects were tested for GBV-C markers in pretransfusion and posttransfusion samples. We estimated the risk of acquiring GBV-C RNA and predictors of GBV-C acquisition, using pooled logistic regression. RESULTS: GBV-C RNA was detected ≤120 days following the first transfusion in 22 (7.5%) of 294 subjects who were GBV-C negative before transfusion. The risk of GBV-C RNA acquisition increased with each unit transfused (odds ratio, 1.09; 95% confidence interval, 1.06-1.11). Lower baseline HIV load and use of antiretroviral therapy were associated with subsequent GBV-C RNA acquisition, after control for units of blood transfused. Leukoreduced status of transfused units was not associated with GBV-C transmission. CONCLUSIONS: Blood transfusion is associated with a significant risk of GBV-C acquisition among HIV-infected patients. Transmission of GBV-C by blood transfusion was inversely related to HIV load.

Human pegivirus viremia in HCV/HIV co-infected patients: Direct acting antivirals exert anti-pegivirus effects.

BACKGROUND: Human pegivirus (HPgV) is a single-stranded RNA virus​ that is closely related to hepatitis C virus (HCV)​. HPgV has also been shown to infect patients with human immunodeficiency virus (HIV). The mechanisms and disease outcomes of HPgV infections are largely unknown, although it has been implicated in both cancer and neurological diseases. There are no established therapies for HPgV. OBJECTIVES: To estimate the prevalence of HPgV in a cohort of HCV/HIV co-infected patients undergoing treatment for HCV with direct acting antivirals (DAA) and investigate the effect of DAA therapy on HPgV infection. STUDY DESIGN: RNA was extracted from plasma samples collected at time points before, during, and after DAA. HPgV RNA abundance was quantified by droplet digital PCR assays targeting the NS5A and 5'UTR domains and confirmed by RT-qPCR. Clinical, demographic and treatment data were analysed. RESULTS: HPgV RNA was detected and quantified in 26 of 100 patients' plasma (26%) before starting DAA. Patients with detectable HPgV were more likely to be male, had higher peak HIV plasma levels, and a history of injection drug use. Patients receiving sofosbuvir/ledipasvir (n = 9) displayed significantly lower HPgV levels at time of DAA completion and had lower post-DAA HPgV rebound​ levels compared to patients receiving sofosbuvir/velpatasvir (n = 11) although both regimens significantly reduced viremia directly following DAA completion. Sustained suppression of HPgV was â€‹also observed among patients (n = 2) receiving pegylated-interferon. CONCLUSIONS: HPgV RNA ​was frequently detected in HCV/HIV co-infected patients and ​was​ supressed by DAA and pegylated interferon therapies with sofosbuvir-ledipasvir showing greatest antiviral activity. These findings suggest potential treatment strategies for HPgV infections​.

GB virus C infection among young, HIV-negative injection drug users with and without hepatitis C virus infection.

Our study examined the association between GB virus C (GBV-C) and (i) hepatitis C virus (HCV) infection status, (ii) biomedical indicators of liver disease (alanine and aspartate aminotransferases) and (iii) HCV RNA level among young injection drug users (IDUs) recruited using street outreach and respondent-driven methods. Cross-sectional and longitudinal analyses were completed. GBV-C (active or resolved) infection was significantly (P < 0.05) more prevalent among HCV antibody-positive (anti-HCV+) (65.1%) than antibody-negative (anti-HCV-) (32.3%) (OR = 3.9, 95% CI: 2.3-6.9) IDUs. The prevalence of resolved GBV-C infection was highest among those with chronic HCV infection (41.9%), followed by those with resolved HCV infection (34.4%) and significantly lower (P < 0.05) among anti-HCV participants (16.9%). Although not statistically significant (P = 0.13), a similar pattern was observed for active GBV-C infection. No association between GBV-C infection status and biomedical indicators of liver disease or HCV RNA level over time was observed. In conclusion, GBV-C infection prevalence was higher among anti-HCV+ compared to anti-HCV- young IDUs, similar to prior studies among older populations. In particular, chronically HCV-infected young IDUs had an increased rate of GBV-C clearance.

How cost-effective is 'No Smoking Day'?

OBJECTIVE: To obtain a more rigorous estimate of the cost-effectiveness of No Smoking Day (NSD), an annual UK-wide campaign to encourage smokers to quit, than has been possible hitherto. DESIGN: Comparison of reported quit attempts in the month following NSD for three consecutive years with adjacent months using repeated national surveys of quit attempts. SETTING: England. PARTICIPANTS: A total of 1309 adults who had smoked in the past year who responded to the surveys in the month following NSD (April 2007-2009) and a comparison group of 2672 adults who smoked in the past year who responded to the survey in the two adjacent months (March and May 2007-2009). MAIN OUTCOME MEASURES: The number of additional smokers who quit permanently in response to NSD was estimated from the survey results. The incremental cost-effectiveness ratio (ICER) was calculated by combining this estimate with established estimates of life years gained and the known costs of NSD. RESULTS: The rate of quit attempts was 2.8 percentage points higher in the months following NSD (120/1309) compared with the adjacent months (170/2672; 95% CI 0.99% to 4.62%), leading to an estimated additional 0.07% of the 8.5 million smokers in England quitting permanently in response to NSD. The cost of NSD per smoker was £ 0.088. The discounted life years gained per smoker in the modal age group 35-44 years was 0.00107, resulting in an ICER of £ 82.24 (95% CI 49.7 to 231.6). ICER estimates for other age groups were similar. CONCLUSIONS: NSD emerges as an extremely cost-effective public health intervention.

Conductance switching in single molecules through conformational changes.

We tracked over time the conductance switching of single and bundled phenylene ethynylene oligomers isolated in matrices of alkanethiolate monolayers. The persistence times for isolated and bundled molecules in either the ON or OFF switch state range from seconds to tens of hours. When the surrounding matrix is well ordered, the rate at which the inserted molecules switch is low. Conversely, when the surrounding matrix is poorly ordered, the inserted molecules switch more often. We conclude that the switching is a result of conformational changes in the molecules or bundles, rather than electrostatic effects of charge transfer.

Effect of antiretroviral therapy and hepatitis c co-infection on changes in lipid levels in HIV-Infected patients 48 weeks after initiation of therapy.

Hepatitis C virus (HCV) commonly co-infects HIV-infected individuals. Antiretroviral therapy (ART) is associated with elevated serum lipid levels, and HCV infection is associated with low serum lipid levels. Fasting lipid levels were investigated in 1,434 ART-naïve HIV-infected people participating in the AIDS Clinical Trials Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) protocol who prospectively initiated ART with 3 agents. Subjects with elevated liver-associated enzymes (>5 x ULN) were excluded. Demographics, body mass index, HCV status, CD4 cell count, HIV RNA, liver enzymes, lipid levels, and glucose were assessed before and following 48 weeks of ART. HCV-positive subjects (n = 160; 11%) were older, more likely to be Black, have a history of intravenous drug use (IDU), have higher baseline liver-associated enzyme levels than the HCV-negative group (p < .001 for each), and to have diabetes at baseline (5% vs. 2%, p = .07). Lipid levels rose in both groups following ART, and the differences were not significant except that HDL levels increased significantly more in the HCV-positive group (p = .006). In summary, HCV infection did not appear to provide significant protection against ART-induced hyperlipidemia in this cohort of HIV-infected subjects prospectively enrolled in ART trials, although HDL levels rose to a greater degree.

Conveying campus sexual misconduct policy information to college and university students: Results from a 7-campus study.

OBJECTIVE: To examine the efficacy of different methods (ie, in-class policy reading; in-class policy reading and discussion; no reading or discussion) to deliver campus sexual misconduct policy information to students on 7 campuses. PARTICIPANTS: A total of 1,195 participants at 7 colleges and universities participated in the study from August to October 2014. Participants were randomly assigned at the class level and completed pretest and posttest surveys assessing knowledge of campus policy and resources and confidence to seek help for sexual assault. RESULTS: Students exposed to a larger dosage of material (in-class policy reading plus discussion) showed greater positive changes in attitudes and knowledge than students who did not receive information or were only read the policy. However, on some indices, students who were only read the policy showed positive outcomes compared with students receiving no intervention. CONCLUSION: Colleges and universities must use engaging methods to disseminate campus sexual misconduct policies to students.

Effective pharmacotherapy of alcoholic amnestic disorder with fluvoxamine. Preliminary findings.

Ten patients with alcoholic chronic organic brain disease were categorized as having alcohol amnestic disorder, or Korsakoff's psychosis (n = 6), dementia associated with alcoholism (n = 3), or compensated alcoholic liver disease (n = 1). All patients had severe deficits in memory for recently acquired information (episodic memory). Patients with alcohol dementia also showed global intellectual decline, including decreased performance on measures of semantic (knowledge) memory and reduction in levels of cerebrospinal fluid somatostatin. In a 4-week double-blind crossover design, the serotonin-uptake blocker fluvoxamine maleate (100 to 200 mg/d) was found to improve episodic memory in only the patients with alcohol amnestic disorder. These improvements in memory were significantly correlated with reductions in levels of cerebrospinal fluid 5-hydroxyindoleacetic acid, suggesting that facilitation of serotonergic neurotransmission may ameliorate the episodic memory failure in patients with alcohol amnestic disorder.

T cells and HIV-induced T cell syncytia exhibit the same motility cycle.

Ameboid cells ranging in complexity from Dictyostelium amebas to human polymorphonuclear leukocytes (PMNs) translocate in a cyclical fashion. Using computer-assisted motion analysis, we have analyzed the motility of human lymphocytes of the immortal SupT1 cell line and of a peripheral blood mononuclear cell population highly enriched for CD4-positive cells (CD4-enriched PBMCs) on four substrates--plastic, dehydrated rat tail collagen, hydrated rat tail collagen, and bovine aortic endothelium. In addition, we have analyzed the motility on these substrates of syncytia induced by human immunodeficiency virus (HIV) in cultures of both cell types. It is demonstrated that both SupT1 cells and CD4-enriched PBMCs exhibit a motility cycle with a period of 1.6 min that is independent of substrate, independent of average cell velocity, and similar to the periods of translocating Dictyostelium amebas and PMNs. More surprisingly, it is demonstrated that HIV-induced SupT1 and PBMC syncytia with volumes 10 to 100 times those of single cells exhibit the same motility cycle as their single-cell progenitors. These observations support the generality of the motility cycle in animal cells and, for the first time, demonstrate that the cycle is independent of cell size.

Physicians' effectiveness in assessing risk for human immunodeficiency virus infection.

An American Medical Association committee recently recommended that physicians routinely screen patients for behaviors that put patients at risk for human immunodeficiency virus infection, yet there is evidence that this screening does not occur routinely. Faculty, fellows, and residents at a teaching hospital in a midwestern state with a low prevalence of acquired immunodeficiency syndrome were surveyed regarding their experience in screening for human immunodeficiency virus, their training related to substance abuse and human sexuality, and their confidence and ease in addressing such topics with their patients. Results indicated that only 11% routinely screened patients for high-risk behaviors. While most physicians had received training in human sexuality, most had not received training in substance abuse screening. Those trained felt more confident in addressing substance abuse and human sexuality and felt more comfortable in caring for patients known to be infected with human immunodeficiency virus. A concerted effort to encourage human immunodeficiency virus risk assessment by physicians is needed. This should include training opportunities in screening and counseling patients about sexual activities and substance abuse.

Testosterone therapy in glucocorticoid-treated men.

BACKGROUND: Treatment with glucocorticoid drugs is a valuable therapy, but the use of these drugs is associated with major side effects, including osteoporosis, muscle wasting, and obesity. In men who take glucocorticoids, circulating testosterone concentrations are reduced, and this might contribute to the changes in bone and soft-tissue mass. OBJECTIVE: To asses the effect of testosterone replacement on these above-mentioned parameters in glucocorticoid-treated men. METHODS: Fifteen asthmatic men who were receiving long-term glucocorticoid treatment were randomly allocated to receive therapy with testosterone esters (30 mg of proprionate, 60 mg of phenylprionate, 60 mg of isocaproate, and 100 mg of decanoate [Sustanon]) (250-mg/mo intramuscular depot injection) or to act as control subjects during 12 months. After a washout period for those men who were receiving testosterone, the groups were then crossed over and studied for a further 12 months. Bone density and body composition were assessed by dual-energy, x-ray absorptiometry. Paired or unpaired 2-tailed t tested were calculated. Unless otherwise stated, all values are given as mean +/- SEM. RESULTS: Bone density in the lumbar spine increased 5.0% +/- 1.4% (mean +/- SEM) (P = .005) during testosterone supplementation, but it did not change during the control period (between-groups difference, P = .05). These changes were accompanied by a decrease in the indexes of bone turnover. There was a gain in body fat mass (2.1 +/- 0.06 kg, P = .01) and a loss of lean body mass (1.4 +/- 0.5 kg, P = .02) during the control period, with both changes being reversed by testosterone treatment (P < .03). CONCLUSION: Testosterone treatment reverses the deleterious effects glucocorticoid drugs on skeletal and soft tissues in men.

Lateral spine densitometry is a more sensitive indicator of glucocorticoid-induced bone loss.

Osteoporosis is a common complication of glucocorticoid therapy. Bone density measurement is now commonly used in assessing which steroid-treated patients require specific interventions to reduce fracture risk. The recently developed techniques for the measurement of bone mineral density (BMD) of the vertebral body alone, by dual-energy x-ray absorptiometry (DXA) in the lateral projection, may be particularly useful in this context since steroid-induced bone loss is most marked in trabecular-rich regions like the vertebral body. This possibility has been assessed in the present study by the measurement of BMD in the lateral and anterioposterior (AP) projections in 28 women receiving chronic glucocorticoid treatment. The two BMD measurements were significantly related (r = 0.62, p < 0.001). When expressed in relation to age-appropriate normal values, lateral BMDs were lower than AP BMDs both in percentage terms (70.8 +/- 4.4 versus 90.3 +/- 2.6%, p < 0.001) and in terms of Z scores (-1.42 +/- 0.22 versus -0.91 +/- 0.24, p = 0.027). AP BMD Z scores classified 12 patients as osteopenic, whereas a further 7 were so categorized by lateral BMD Z score. It is concluded that lateral DXA scanning is a more sensitive indicator of glucocorticoid-induced osteopenia than conventional BMD measurement in the AP projection.

Sources of interracial variation in bone mineral density.

Many studies have demonstrated significant differences in bone mineral density between various racial groups. Although it has been suggested that differences in body weight contribute to such interracial variation, the artifactual effect of the skeletal size inherent in projectional absorptiometry methods has been largely ignored. We have measured bone mineral density by dual-energy X-ray absorptiometry in the lumbar spine and at three femoral sites in 200 premenopausal women of Chinese, Indian, European, or Polynesian origin (50 of similar mean age in each group). In the Chinese and Indian women the measured bone mineral density measurements (g/cm2) were similar, but significantly less, at all sites, than those of European women (p < or = 0.005). The European women were, however, significantly taller than both the Chinese and Indian women (p < 0.0001), and when the scale artifact of absorptiometry was removed by dividing the measured bone mineral density either by the height of the subject, or by the square root of the area over which the X-ray beam was projected, then the differences in mean bone mineral density between the Chinese, Indian, and European women were almost completely eliminated. The Polynesian women were significantly more obese (as judged from mean body mass index) than all the other groups (p < 0.0001) and had significantly greater bone mineral density at all sites than all the other groups both before (p < 0.0001) and after (p < 0.0001) correcting for the scale artifact.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of the anti-estrogen tamoxifen on cardiovascular risk factors in normal postmenopausal women.

There is growing interest in the use of anti-estrogens as agents of disease prevention. Studies of women with breast cancer suggest that the synthetic anti-estrogen tamoxifen may reduce the incidence of cardiovascular disease, but the effects of this agent on cardiovascular risk factors in healthy women have not been studied. We have performed a two-year, randomized, placebo-controlled trial to assess the effects of tamoxifen 20 mg/day on serum lipids, fibrinogen, and body composition in 57 normal postmenopausal women. Tamoxifen treatment lowered levels of serum cholesterol by (mean +/- SE) 12 +/- 2%, low density lipoprotein cholesterol by 19 +/- 3%, and fibrinogen by 18 +/- 4% (P < 0.0001 vs. placebo for each). Levels of high density lipoprotein cholesterol were not altered by tamoxifen, but the ratio of total cholesterol to HDL-cholesterol decreased by 11 +/- 4% (P < 0.001 vs. placebo). Tamoxifen did not affect levels of triglycerides, high density lipoprotein cholesterol subfractions, apolipoprotein A1, or glucose, and did not change body weight, body mass index, or body fat distribution. We conclude that tamoxifen significantly reduces the levels of atherogenic lipids and fibrinogen in normal postmenopausal women. The results suggest that the anti-estrogens may substantially reduce the risk of cardiovascular disease, which remains the most common cause of death among postmenopausal women.